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Does Erythropoietin Improve Outcome in Very Preterm Infants?

This study has been completed.
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
Bucher Hans Ulrich, Swiss Neonatal Network
ClinicalTrials.gov Identifier:
NCT00413946
First received: December 18, 2006
Last updated: May 19, 2014
Last verified: May 2014

December 18, 2006
May 19, 2014
January 2006
March 2012   (final data collection date for primary outcome measure)
Mental developmental index (Bayley II) and motor, visual and hearing impairment [ Time Frame: at age of 24 months corrected for prematurity. ] [ Designated as safety issue: No ]
  • and motor, visual and hearing impairment at 24 months corrected for prematurity.
  • assessed with ultrasound and MRI, mental developmental index (Bayley II)
  • incidence and severity of intracranial haemorrhage and white matter disease
Complete list of historical versions of study NCT00413946 on ClinicalTrials.gov Archive Site
  • MRI at term equivalent [ Time Frame: 40 postmenstrual weeks ] [ Designated as safety issue: No ]
    White matter injury score grey matter injury score brain maturation
  • cerebral palsy. [ Time Frame: First 24 months of life (corrected for prematurity) ] [ Designated as safety issue: No ]
  • Cognitive development and cerebral palsy [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    Kaufmann ABC II, standardized neurological, visual and hearing examination, questionnaire about health status and behavior.

    Classification of impairments, disabilities and handicaps.

Not Provided
Not Provided
Not Provided
 
Does Erythropoietin Improve Outcome in Very Preterm Infants?
Neuroprotective Effect of High Dose Erythropoietin in Very Preterm Infants

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in very preterm infants improves neurodevelopmental outcome at 24 months corrected age.

This study is designed as randomized, double-masked, placebo controlled multicenter study involving at least 420 patients.

HYPOTHESIS Early administration of human erythropoietin (EPO) in very preterm infants reduces perinatal injury to the brain (retina), lung and gut and improves neurodevelopmental outcome at 24 months corrected age.

PRIMARY OBJECTIVE To determine whether cerebral outcome is improved if infants born between 26 0/7 and 31 6/7 gestational weeks at birth receive erythropoietin in high dose in the first three days after birth.

SECONDARY OBJECTIVES To determine whether early administration of EPO alters the incidence of complications typically associated with preterm birth, i.e. mortality, septicaemia, necrotising enterocolitis, bronchopulmonary dysplasia (oxygen dependency at 36 weeks postmenstrual age), retinopathy, intracranial haemorrhage, white matter disease (periventricular leucomalacia), growth failure, cerebral palsy and handicap at 5 years.

Biomarkers of encephalopathy of prematurity assessed on magnetic resonance imaging (MRI) at term equivalent age.

RATIONALE EPO has been shown to be protective against hypoxic-ischaemic and inflammatory injuries in a broad range of tissues and organs besides promoting red cell formation. It has been shown to have neuroprotective and neurotrophic activity in animals after acute brain damage as well as in adult stroke patients. Several mechanisms explaining this activity have been recognized: EPO inhibits glutamate release in the brain, modulates intracellular calcium metabolism, induces the generation of anti-apoptotic factors, reduces inflammation, decreases nitric oxide-mediated injury, and has direct antioxidant effects.

Very preterm infants have significant delay in mental and physical development assessed at 24 months corrected age. The most critical period are the first days after preterm birth where the oxygenation of the brain may be impaired by respiratory, circulatory and nutritional insufficiency. Although there are probably several mechanisms involved in permanent brain damage, it is most likely that EPO with its multiple action may reduce this damage.

EPO has been studied in several trials in preterm infants to prevent anaemia and is now widely used for this indication.

STUDY DESIGN Randomized, double-masked, placebo-controlled multicenter clinical trial. Research plan 420 infants will be randomized during the first three hours of life to receive EPO (3000 U/kg body weight) or placebo intravenously at 3, 12-18 and 36-42 hours after birth. Standardized evaluation including cerebral sonography at day 1 and 7 and at 36 0/7 gestational weeks (or at discharge home if discharged before) will determine the presence or absence of complications. Cerebral volume and white matter volume will be assessed at 40 postmenstrual weeks with MRI (only if available).

Experienced examiners will assess developmental function at 24 months corrected age using the reliable and validly revised Bayley Scales II of Infant Development and determine the presence or absence of impairment of motor function (cerebral palsy) and neurosensory function (blindness or deafness).

CLINICAL SIGNIFICANCE At least 1 of every 100 live born infants is born very preterm. 90% of these infants survive but >50% have a delay in mental and physical development assessed at 24 months corrected age. More subtle problems affecting cognition, vision and hearing are common at the age of five years and have an impact on school performance and quality of life of the infants and their families. The aim of this trial is to examine whether a short, easily applicable and well tolerated pharmacological intervention can improve neurodevelopmental outcome.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Intracranial Hemorrhage
  • Periventricular Leukomalacia
  • Cerebral Palsy
  • Neurodevelopmental Delay
Drug: Recombinant human Erythropoietin
3 doses 3000 units (1 ml) of rEpo or 1 ml of saline per kg body weight
  • Experimental: rEpo
    Three doses of rEryhtropoietin (3000 U/kg body weight) intravenously at 3, 12-18 and 36-42 hours after birth.
    Intervention: Drug: Recombinant human Erythropoietin
  • Placebo Comparator: saline
    Three doses of placebo (0.9% saline 1 ml/kg body weight) intravenously at 3, 12-18 and 36-42 hours after birth
    Intervention: Drug: Recombinant human Erythropoietin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
420
March 2012
March 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Infants born between 26 0/7 and 31 6/7 gestational weeks
  • Postnatal age less than 3 hours
  • Informed parental consent (preferably obtained before birth)

Exclusion Criteria:

  • Genetically defined syndrome
  • Severe congenital malformation adversely affecting life expectancy
  • Severe congenital malformation adversely affecting neurodevelopment
  • A priory palliative care
  • Intracranial haemorrhage grade 3 or more detected before dose 3 of Erythropoietin
Both
up to 3 Hours
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00413946
3200B0-108176, RoFAR ID 2127989593, 3200B0-108176
Yes
Bucher Hans Ulrich, Swiss Neonatal Network
Swiss Neonatal Network
Swiss National Science Foundation
Principal Investigator: Hans U Bucher, Prof University of Zurich
Swiss Neonatal Network
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP